Hydrazones of 1-amino-4-dibenzocycloheptenylpiperazines



ferred to above include fluoroph'enyL' United States Patent ABSTRACT OFTHE DISCLOSURE Hydrazones derived from 1-amino-4-(dibenzocyclohleptenyl'and dibenzocyclyooctenyl)piperazines and a variety of aldehydes andketones are described herein. These hydrazones are useful asanticonvulsan't agents. They are usually'prepa'red by the reaction of anaminopiperazine with an aldehyde or ketone.

The present application is a continuation-in-part of application Ser.No. 362,929, filed Apr. 27, 19'64,'and now US. Patent 3,290,300.

The present invention relates to a group of compounds which arehydrazones derived from 1-amino-4- dibenzocycloheptenylpiperazines and avariety of aldehydes and ketones. More particularly, the presentinvention relates to compounds having the following general formulawherein X is selected from the group consisting of hydrogen, methyl andhalogen; Y is selected from the group consisting of lower 'alkylenecontaining from 2 to '3 carbon atoms inclusively'; Z is selected fromthe group consisting of vinylene and lower alkylene containing from 2 to3 carbon atoms inclusively; m and n are each a'whole number between 0'and 1 inclusive; =CRR' is 1-methyl-4-pipe'ridylidene, 9-fiuorenylid'ene,or, individually, R is methyl, phenyl, substituted phenyl, pyridyl, orsubstituted pyridyl and R is selected from phenyl, hydroxyphenyl,,methoxyphenyl, methylenedi 'oxyphenyl, cyanophenyl, pyridyl,methylpridyl, ethylpyn'dyl, hydroxypridyl, and N-oxides of the aforesaidpyridyl groups. A particularly preferred embodiment of this inventionare those compounds wherein R is hydrogen and R ,is pyridyl,,methylpyridyl, or the N-oxides of these pyridyl radicals. The halogensreferred to above include fluorine, chlorine, bromine, and iodine. Thehalophenyl' radicals frechlorophen'yl, bromophenyl, and iodophenyl.

Y and Z are restricted to those values of lower alkylene in which thefree valences are of different carbon atoms, and it isparticularlypreferred to have the free 3,377,344 Patented Apr. 9, 1968valence on the terminal carbon atoms. Thus, ethylene and trimethyleneare particularly preferredalkylene values for these groups. Thecompounds of this invention are useful because of their pharmacologicalactivity. More specifically', the'secompounds are useful because oftheir anti-convuls ant activity. 'Dhus,' like diphenylhydantoin, theyantagonize electroshock seizures. "In addition,"'they show" activityagainst convulsions induced by pentylenetetrazol.

The organic bases of this invention form nontoxic acid addition saltswith a variety of organic and inorganic acids. Such salts are formedwith acid'ssuch as' sulfuric, phosphoric, hydrochloric, 'hydrobromic,

hydriodic, sulfamic, citric, lactic, maleic; malic, succinic,

tartaric, cinna-mic, acetic, and related acids.

The compounds of this invention are conveniently prepared by thecondensation of'an aldehyde or ketone with a hydrazine of the followinggeneral structure wherein X, Y, Z, m and n are defined as above. Thereaction is conveniently carried out inaninert solv'ent.

'benzoic, gluconic, ascorbic,

Thatis, the reaction'iscarried out in a solvent 'which will not reactwith'the 'aldehyde, ketone, or hydrazine used. Useful solvents for thisreaction are alcohols such as ethanol and 2-propanol and aromatichydrocarbons such as benzene and toluene. The reaction can optionally becarried out in the presence of 'alsmall amount of: acid "which serves topromote the reaction. Acetic acid is an example of an acid usefulforthis "purpose.

Although aldehydes and ketones' are the'most convenient startingmaterials for use in this reaction, carbonyl derivatives are alsouseful. For example, it is possible to use acetals, ketals, diacetates,and other carbonyl deregard are compounds such as N-(fldimethylarninophenyl) -oz (N-oxidopyridyl )nitrones.

The following examples are presented to further .illustrate the presentinvention; they should'not be construed as limiting it in spirit or inscope. *Inth'ese examples, quantities are indicatedin parts by weightunless parts by volume are indicated and temperatures are given indegres cent-i'grad'e 'C;). The relationship between partsby' volume andparts by weight is the same' as that between milliliters and grams.

EXAMPLEI A solution of 38 parts of 2-ChlO1'O-10,1l'dihYdIOrSH-dibenzo[a,d],cyclohepten:5-one in v17-"5fpa'1'ts. of ether is addedportionwisrto a stirred mixture of .10 parts of lithiumaluminu'mhydridein .525 parts of ether. After the zidditiionis complete, themixture is refluxed .for .2

' 3 hours. It is then cooled in an ice bath and decomposed by thecautious addition of (1) 15 parts. of water in 27 parts oftetrahydrofuran, (2) 5 parts of sodium hydroxide in parts of water, and(3) 35 parts of water. The resultant mixture is filtered and the saltsseparated in this way are washed with ether. The resultant filtrate isthen dried and the solvent is evaporated under reduced pressure to leavea residual oil which solidifies. The product obtained in this way is 2chloro-10,1l-dihydro-SH-dibenzo[a,d]cyclohepten-5-ol melting at about90-92 C.

A solution of 36 parts of2-ch1oro-10,1l-dihydro-SH-dibenzo[a,d]cyclohepten-5-ol in 375 parts ofchloroform is prepared. Hydrogen chloride gas is then bubbled throughthis solution for minutes and then nitrogen gas is bubbled through thesolution to remove excess hydrogen chloride. The solution is then driedand the solvent is evaporated under reduced pressure to leave a residualoil. Trituration of this oil with hexane gives a solid which melts atabout 96-97 C. after recrystallization from hexane. The product obtainedin this way is 2,5-dichloro- 10,1 l-dihydro-SH-dibenzo a,d]cycloheptene.

EXAMPLE 2 To a solution of 200 parts of homopiperazine in 100 parts ofwater is added 450 parts of concentrated hydrochloric acid over a periodof minutes while the temperature is maintained at about -45 C. Thesolution is then cooled to 0 C. and a solution of 141 parts of sodiumnitrite in 280 parts of water is added portionwise while the temperatureis maintained at 0-5 C. The mixture is stirred for an additional 15minutes after the addition is complete, and then cooled in an ice bath.A solution of 1000 parts of aqueous sodium hydroxide solution is addedportionwise While the temperature is maintained below 25 C. The oilylayer which forms is separated and the aqueous layer is extracted withchloroform. The oily layer and the chloroform extracts are thencombined, dried, and distilled to give l-nitrosohomopiperazine boilingat about 110-115 C. at 0.2 mm. pressure.

If the above procedure is repeated using 2,5-dimethylpiperazine as thestarting material for the nitrosation, the product obtained is1-nitroso-2,S-dimethylpiperazine boiling at about 120 C. at 0.3 mm.pressure. This material :solidifies to give a product melting at about7374 C.

EXAMPLE 3 A mixture of 23 parts of5-chloro-10,ll-dihydro-SH-dibenzo[a,d]cycloheptene, 12 parts ofl-nitrosopiperazine, 20 parts of potassium carbonate, 5 parts of sodiumiodide, 'and 320 parts of 2-butanone is stirred and refluxed for 16hours. The resultant mixture is filtered to remove salts and the solventis evaporated from the filtrate under reduced pressure. The resultantresidue is dissolved in chloroform and the chloroform solution is washedwith water and dried and the" solvent is evaporated under reducedpressure to leave a crystalline residue. Ether is added to this residuewhich is then filtered. The product obtained in this way is1-(10,ll-dihydro-SH-dibenzo[a,d] cyclohepten 5-yl)-4-nitrosopiperazineand it melts at about 193-194 C. after recrystallization from a mixtureof chloroform and ether.

A solution of 21 parts of the above nitroso compound in 280 parts ofhot'tetrahydrofuran is added portionwise, with stirring, to asuspensionof 8 parts of lithium aluminum hydride in 420 parts of tetrahydrofuran.This addition is carried out over a period of 1 hour at a temperature of40-45" C. The mixture is then heated for 2 hours at 4550 C. before it iscooled in an ice bath and decomposed by the cautious dropwise additionof water. The reaction mixture is filtered to remove precipitated saltsand the solvent is evaporated from the filtrate to leave a residualsolid which is mixed with ether and then filtered. The product thusobtained is 1-(10,1l-dihydro-SH-dibenzo[a,d]cyclahepten-S-yl)-4-aminopiperazine and it melts at about145146, C. after recrystallization from a mixture of chloroform andhexane. This compound has the following formula CHN CH2 1 If anequivalent quantity of 2,5-dichloro-10,1l-dihydro- 5Hdibenzo[a,d]cycloheptene is substituted for the 5-chloro-10,1l-dihydro-SH-dibenzo[a,d]cycloheptene in the proceduredescribed in the preceding two paragraphs, there is first obtained1-(2-chloro-10,1l-dihydro-SH-dihehzo-[a,d]cyclohepten-5-yl)-4-nitros0piperazine which is then reduced to give1 (2-chloro-10,1l-dihydro-SH-dibenzo-[a,d]cyclohepten-S-yl)-4-aminopiperazine.

In a similar manner,3,5-dichloro-10,1l-dihydro-SH-dibenzo[a,d]cycloheptene reacts withl-nitrosopiperazine to give 1(3-chloro-10,1l-dihydro-SH-dibenzo[a,d]cyclohepten 5yl)-4-nitrosopiperazine melting at about 187-188" C. Reduction of thisnitroso compound with lithium aluminum hydride according to theprocedure described above gives 1(3-chloro-10,1l-dihydro-SH-dibenzo[a,d]cyclohepten-S-yl)-4-aminopiperazinemelting at about 157-l58 C. after recrystallization from a mixture oftetrahydrofuran and hexane.

Likewise, the reaction of2-methyl-5-chloro-10,1l-dihydro-SH-dibenzo[a,d]cycloheptene withl-nitrosopiperazine according to the procedure described in the firsttwo paragraphs above first gives 1-(2-methyl-l0,l1-dihydro 5Hdibenzo[a,d]cycloheptcn-5-yl) 4 nitrosopiperazine and then, onreduction, 1-(2-methyl-10,11- dihydro-SH-dibenzo[a,d]cyclohepten 5 yl) 4aminopiperazine.

If l-nitrosohomopiperazine is substituted for the l-nitrosopiperazineand the procedure of the first two paragraphs of this example isrepeated, there is obtained first, l-(lO,1l-dihydro-SH-dibenzo[a,d]cyclohepten 5-yl)-4-nitrosohomopiperazine, andthen 1-(10,1l-dihydro-Sl-I-dibenzo-[a,d]cyclohepten-5-yl-4-aminohomopiperazine.

EXAMPLE 4 A solution is prepared from 45 parts of 5-chloro-5H-dibenzo[a,d]cycloheptene and 560 parts of Z-butanone. To this solutionis added 55 parts of potassium carbonate and then 24 parts ofl-nitrosopiperazine. This mixture is allowed to stir at room temperaturefor about 23 hours and then refluxed for 3 hours. It is then filteredand the solvent is evaporated from the filtrate under reduced pressureto leave a residual solid. Ether is added to the residue which is thenfiltered to give 1-(5H-dibenz0[a,d]cyclohepten-S-yl)-4-nitrosopiperazine melting at about 184-195 C.

A solution of 26 parts of the above nitroso compound in parts oftetrahydrofuran is added dropwise with stirring to a suspension of 10parts of lithium aluminum hydride in 765 parts of tetrahydrofuran. Theaddition takes place at about 30 C. over a period of about 25 minutes.The mixture is then stirred at this temperature for an additional 15minutes before it is cooled to about 5 C. and decomposed by the cautiousdropwise addition of (1) 15 parts of Water in 27 parts oftetrahydrofuran, then (2) 10 parts of sodium hydroxide in 20 parts ofwater, and finally (3) 25 parts of water. The mixture is then filteredand the separated salts are washed with hot tetrahydrofuran. Thefiltrate is dried and the solvent is evaporated under reduced pressureto leave a residual solid. This solidis mixed with hexaneand thenfiltered to give 1 (5H dibenzo[a,d] cyclohepten-S-yl)-4-aminopiperazinemelting at about -167" C.

batch, semi-continuous or continuous and mixtures of thiobis compoundsare useful.

To avoid oxidation, the treatment is generally conducted under a blanketof inert gas such as nitrogen, carbOn dioxide, steam and the like.

The disproportionation and bleaching achieved by the method of theinvention are surprising results since the effects are simultaneous andit would not be expected that the treating compounds, some of which areknown antioxidants, would be disproportionation catalysts as well asbleaching agents. In this regard, the invention is distinguished fromthat of copending application Ser. No. 579,- 819 filed Sept. 16, 1966,which describes bleaching of rosin compounds with the treating compoundsin that the conditions of treatment in the latter case are lessstringent and involve little or no transformation of abietic acid ascompared with the present invention wherein abietic TABLE I Example FeedProduct Feed Product TBP, percent 0.1 0. 4 Abietie Acid, percent. 30. 53. 0 30. 5 1. 7 Color X 4A 2A 3A EXAMPLES 3-4 TABLE II Example 0.1K TBP0.5K TBP Time, Hrs.

Abletic Acid Dehydro- Abietic Acid Dehydro- Percent abeitie Acid ColorPercent abietie Acid, Color Percent Percent 2. 6 31. 8 3A 1. 2 34. 7 2A1.0 33.8 WG 0.8 33.9 X 0. 7 36. 6 WG 0. 7 35. 3 X 0.7 36.1 WG 0. 8 36. 2WW acid is reduced to less than about by weight of the rosin.

The following examples further illustrate the invention but are notlimitative thereof except as indicated in the appended claims. All partsand percentages are by weight unless otherwise specified.

EXAMPLES 5-6 In essentially the same manner as in Examples 14, the sametype rosin was heated at 300 C. with 0.2% of the thiobisphenolsindicated in Table III for 6 hours with sampling after each 2 hours foracid and color analyses. Good disproportionation and bleaching resultedin each instance.

TABLE III Time, hours, Abeitie Acid, Dehydro- Feed Percent- 31.2 abietieAcid, Color, Y

Percent Example 54,4-thiobis(6tert-butyl-meta eresol) 2 9. 4 22. 4 6A 47. 1 41. 4 6A Example 64,4-thiob1s(6-tert-buty10rtho cresol) 2 9.0 24. 06-A7A 4 6.1 30. 7 (SA-7A EXAMPLES 1-2 The data of Table I is based onreactions conducted substantially as follows:

To a suitable reaction vessel was charged tall oil rosin conforming tothe Naval Stores Act (Feb. 8, 1952) and Federal SpecificationLLL-R-6266, Class C (May 27, 1957), except for less bottoms content. Tothis was added the indicated amount of TBP, i.e., 2,2'-thiobis(4-methyl- 6-t-butylphenol). The mixture was then heated at 300 C. for 5hours. The data shows effective disproportionation and bleaching.Abietic acid content was determined by UV and the colors are based onthe conventional French scale wherein 4A represents four grades lighterthan X and 3A is one grade lighter than 2A.

EXAMPLES 7-8 Table IV below demonstrates effective disproportionation oftwo mixtures containing rosin. Example 7 is a mixture of 55 parts of atall oil fraction of typical analysis 94.2% fatty acids, 4.2% rosinacids, and 1.6% unsaponifiables, and 45 parts of the same type rosin asin Examples 1-6. Example 8 mixture is a crude tall oil distillate havingthe indicated analysis. Temperature of treatment was 300 C., 0.2% of2,2'-thiobis(4-methyl-6-t-butylphenol was employed in each example, andtreatment was effected under a cover of steam rather than nitrogen. Gooddisproportionation resulted in both instances. GLC refers to agas-liquid chromatographic analysis.

TABLE IV Example Feed 2 His. 4 Hrs. 6 Hrs. Feed 2 Hrs. 4 Hrs. 6 Hrs.

GLO Analyses:

Oleic Acid, percent 25.7 31.3 32.6 33.6 26.0 28.7 28.4 31.6 Linoleic:

Conjugated, percent 7. 12.5 10. 8.3 6.1 11.1 0. 3 8.1Non-Conjugated,percent..- 20.9 7.2 4.9 4.4 20.1 8.0 5.9 5.0 AbieticAcid, percent 12. 1 0. 5 0.0 0. 0 12. 7 0.5 0.0 0. O DehydroabieticAcid, pcrcent- 9. 9 24. 0 26. 2 28. 2 3. s 21. 2 24. 7 25. 4

EXAMPLES 915 EXAMPLES 19-20 h e Exam 1 1-6 and the T 011 msm of t e p esExample 19 of Table VII below show comparatlve reindicated amount of 2,2-th1ob1s(4methyl-G-t-butylsults when the rosin type of Example 1 1sdisproportion- Phenol) were charged flask equPPed ated by heating for 6hours with the thiobis henol (TBP) with a gas inlet tube, thermometer,agitator and conof Exam 161 and when to p t d denser. The temperaturewas raised to approximately p ISPO p lonalon F Q 3 C under nitrogen andthen steam Substituted far the under the same cond1t1ons with the knownantioxidant I I a e l nitrogen. The dlsproportionation was earned out atthe MBP, 'methylenetilsw'mgthyl'6'tert'butylph? temperature andconcentrations noted in Table V. The Good dlspmpol'tlonatlon Over thecontrol (T031n reaction was l d i di ll d disproportionation heatedunder same CODdlUOnS without additive) is evident followed by UVanalysis. Good disproportionation and in the case of'treatment in thepresence of TBP but bleaching is evident from the results (shown inTable V). essentially no benefit results when MBP is employed.

TABLE V 'lempera- Concentra- Time, AbieticAcid, Dehydro- Example ture,0., tion percent Hours percent, 30. 2 AbieticAcid, Color Y Feed percent9 310 0.1 2 3.1 31.6 5.1 4 1.5 34 9 4A 5 1.3 35.2 4A 10 300 0. 1 2 6. 125. 7 6A 4 3.3 31.4 6A 5 2.3 33.5 4A 11 300 0. 4 1 5. 6 25.6 6A 3 2.229.8 5A 5 1.5 25.9 3A 5 1.0 32.1 3.1 12 300 0.2 1 9.3 7A 3 3.5 6A7A 52.5 20.3 6A-7A 6 1.7 28.8 6A 13 285 0.4 i 0 4:1 l 25. 7 'oX-sX 14 350 0.1 A 2.8 34.

1 1.1 35. 7 WW-WG 1% 0.3 39.3 2 0.3 39.2 WW-WG 15 350 0. 5 *0 5. 9 2e. 7e14 1.2 347 2A 1 0.3 33.9 X 1% 0.7 35.3 X 2 0.8 36.2 WW

*Sample taken as soon as a temperature of 350 C. was reached.

EXAMPLES 15-13 Table VI shows the effective disproportionation andbleaching of other rosin types. Conditions of treatment were essentiallythe same as in the foregoing examples except as indicated. The catalystWas 2,2-thiobis(4- methyl 6 t butylphenol). Acid analysis was by UV. Thetall oil S-l type rosin is a commercialy available rosin substantiallythe same as that identified in Example 1 except that it contains somebottoms.

TABLE VI Concentra- Abietic Dehydra- Example Temp, tion, Time, Acid,abietic Color C. percent hours percent Acid,

percent 1 Feed 14. 0 K 16Gum Rosin 300 0. 1 2 3. 9 20. 3 N 5 2. 4 22. 2N Feed 42. 6 M 17Wood Rosin 300 0. 1 f; 3 .5 2. 3 27. ii WG-N Feed 29. 920. 2 18-1al1 on, 3-1 115515 210 0.1 i i g 55 Example 6 to give thecorresponding hydrazone in each instance. Thus,6-methylpyridine-Z-carboxaldehyde reacts with the hydrazine to give1-(10,1l-dihydro-SH-dibenzo- [a,d]cycloheptenyl)-4-(6-methyl-2-pyridylmethyleneamino)-piperazine melting at about139-140 C. after recrystallization from hexane.3-methylpyridine-2-carboxaldehyde reacts with the hydrazine to give1-(10,lldihydro-SH-dibenzo [a,d] cyclohepten-S-yl) -4- 3-methyl-2-pyridylmethyleneamino)piperazine melting at about 125 C. afterrecrystallization from a mixture of benzene and hexane.3-methylpyridine-4-carboxaldehyde reacts with the aminopiperazine togive 1-(10,11-dihydro-5H-dibenzo [a,d] cyclohepten-S-yl -4-(3methyl-4-pyri lylmethyleneamino)piperazine melting at about 208-210 C.after recrystallization from a mixture of chloroform and hexane. In thesame reaction, 5-ethylpyridine-2-carboxaldehyde gives 1 (10,11dihydro-5H-dibenzo[a,d]cyclohepten-5- yl -4- (5-ethyl-2-pyridylmethyleneamino piperazine melting at about 182183 C.after recrystallization from a mixture of benzene and hexane. Thehydrazone obtained with 3-hydroxypyridine-2-carboxaldehyde is1-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-4-(3 hydroxy-Z-pyridylrnethyleneamino)piperazine melting at about 240243 C. afterrecrystallization from a mixture of chloroform and hexane.

EXAMPLE 20 5 parts of N-(4-dimethylaminophenyl)-a-(1-oxido-4-pyridyl)nitrone'is slurried with 25 parts of water and then acidifiedwith 25 parts by volume of 3 N hydrochloric acid. An additional parts ofwater is added to the mixture. Then, a solution of 5.7 parts of1-(10,11-dihydro 5H dibenzo[a,d]cyclohepten 5 yl) 4 aminopiperazine inparts by volume of 3 N hydrochloric acid is added to the mixture. Ayellow precipitate forms. This is separated by filtration and washedwith cold water. The solid is then slurried in water and benzene and themixture is made neutral with dilute potassium carbonate solution. Thebenzene layer is then separated, washed with water, and dried, and thesolution is concentrated to a small volume at reduced pressure. Ether isadded to the resultant concentrate which is then cooled to give crystalsof 1-(l0,1l-dihydro-SH-dibenzo[a,d]cyclohepten 5 yl) 4 [(1 oxido 4pyridyl)methyleneamino]piperazine. This compound melts at about 189- 190C. and it has the following formula place of the l-oxidopyridylstructure in the compound described above.

EXAMPLE 21 An equivalent quantity of 1-methyl-4-piperidone issubstituted for the piperonal and the procedure of Example 6 is repeatedto give 1-(10,1l-dihydro-SH-di-benzo[a,d] cyclohepten 5 yl) 4 (1 methyl4 piperidylideneamino) piperazine melting at about 173174 C. afterrecrystallization from a mixture of benzene and ether.

EXAMPLE 22 A mixture of 5 parts of 1-(fiuoren-9-ylideneamino)piperazine, 4.5 parts of S-chloro-SH-dibenzo[a,d]cycloheptene, 10 partsof potassium car-bonate, and 200 parts of acetone is stirred at roomtemperature for 19 hours. The mixture. is filtered to remove salts andthe resulting solution is concentrated to a small volume at reducedpressure. Hexane is added to the resultant concentrate which is thencooled to give crystals of I-(SH-dibenzo- [a,d]cyclohepten 5 yl) 4(fluoren 9 ylideneamino) piperazine. This compound melts at about174-176 C. after recrystallization from a mixture of chloroform andhexane. 7

What is claimed is:

1. A compound of the formula wherein X is selected from the groupconsisting of hydrogen, methyl, and chlorine; Y is lower alkylenecontaining from 2 to 3 carbon atoms inclusively and separating thenitrogen atoms attached thereto by at least 2 carbon atoms; Z isselected from the group consisting of vinylene, ethylene, andtrimethylene; m and n are each a whole number between 0 and 1 inclusive;Q is selected from the group consisting of 1-methyl-4-piperidylidene,9-fluorenylidene and =CRR' wherein R is selected from the groupconsisting of methyl, phenyl hydroxyphenyl, methylenedioxyphenyl,cyanophenyl, pyridryl, methylpyridyl, ethylpyridyl, N-oxides of theaforesaid pyridyls, and hydroxypyridyl; and R is selected from the groupconsisting of hydrogen and methyl.

2. A compound according to claim 1 which has the formula formula 4. Acompound according to claim 1 which is 1-( 10, 11 dihydro 5Hdibenzo[a,d]cyclohepten 5 yl) 4- (2-pyridylmethyleneamino)piperazine.

11 12 5. A compound according to claim I which has the 10. A compoundaccording to claim 1 which has the formula formula 11. A compoundaccording to claim 1 which is l-(lO,

11 dihydro 5H dibenzo[a,d]cyclohepten 5 yl) 4-(4-pyridylmethy1eneamino)homopiperazine.

12. A compound according to claim 1 which has the formula 6. A compoundaccording to claim 1 which is l-(SH- dibenz0[a,d]cyclohepten 5 yl) 4 (4pyridylmethyl- 2O eneamino piperazine.

7. A compound according to claim 1 which has the f 1 CH ormu a l 2 l mCH: CHN I NN=OH l CH3 \N/ 13. A compound according to claim 1 which is1-(5,6, 7,12 tctrahydrodibcnzo[a,d]cycloocten 12 yl) 4 (4-pyridylmethyleneamino piper-azine.

14. A compound according to claim 1 which is 1-(10, O1 11 dihydro SHdibenzo[a,d1cyclohepten 5 yl) 4- (6 methyl 2pyridylmcthylenearnino)pipcrazinc.

15. A compound according to claim 1 which is 1-(10, 11 dihydro 5Hdibcnzo[a,d]cycloheptcn 5 yl) 4- [(1 oxido 4pyridyl)methyleneamino]pipcrazine.

8. A compound according to claim 1 which is l-(2- References Citedchloro 10,11 dihydro 5H dibenzoimdlcyclohcptem 5 yl) 4 (4pyridylmethyleneamino )piperazine. UNITED STATES PATENTS 9. A compoundaccording to claim 1 which is 1-(3- 3,290,300 12/1966 Cusic et al 260240chloro 10,11 dihydro 5H di'benzo[a,d]cyclohepten- 4 5 -yl) -4-(4-pyridylmcthyleneamino) piperazine.

JOHN D. RANDOLPH, Primary Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No.3,377,344 April 9, 1968 John W. Cusic et a1.

It is certified that error appears in the above identified patent andthat said Letters Patent are hereby corrected as shown below:

Column 5, line 13, "cyclopentene" should read cycloheptene Column 7,line 32, cancel "more".

Signed and sealed this 20th day of January 1970.

(SEAL) Attest:

Edward M. Fletcher, Jr.

Attesting Officer Commissioner of Patents WILLIAM E. SCHUYLER, JR.

